Our general objective is to understand how perinatal exposure of a mouse to antibody against one of the immunoglobulin allotypes coded for in its genome can suppress, for longer or shorter periods, production of that allotype. These studies may give some insight into the process of differentiation of the immune system and the normal regulation of immunoglobulin synthesis. Specifically we aim to: 1) Understand the mechanism by which perinatal exposure of BALB/c x SJL hybrid mice to anti-allotype antibody results in the generation of thymus-derived (T) cells capable of suppressing synthesis of the target allotype for the life of the hybrid. 2) Understand the mechanisms through which the suppressor T-cells are able to prevent normal bone-marrow derived (B) cells from differentiating to cells which produce the target immunoglobulin. 3) Determine whether similar mechanisms operate in other hybrids and inbred strains where allotype suppression as a result of perinatal exposure to anti-allotype antibody is short lived, that is, where the animals recover and produce normal allotype levels after approximately 12 weeks of age. 4) Understand the nature of the genetic contribution from SJL which predisposes SJL x BALB/c hybrids to chronic rather than short-term suppression. BIBLIOGRAPHIC REFERENCES: Herzenberg, Leonore A., Ko Okumura, and Leonard A. Herzenberg. 1975. Mecahnism of allotype suppression. In Suppressor Cells in Immunity, Proceedings of International Symposium, Eds: S. K. Singhal, N.R. St. C. Sinclair. University of Western Ontario, London, Ontario, Canada, May 12-14, 1975. P. 93. Herzenberg, Leonore A., Ko Okumura, and Leonard A. Herzenberg. 1975. Regulation of Immune Response by Cooperator and Suppressor T Cells. Presented at the 10th Leukocyte Culture Conference, Amsterdam, The Netherlands, September 10-13, 1975. (Abstract).